Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Nanomedicine (Lond). 2012 May;7(5):651-62. doi: 10.2217/nnm.11.151.
Coupling of capsular polysaccharides of pathogens to immunogenic protein carriers (conjugate vaccines) improves carbohydrate immune response. Our idea is to explore gold nanoclusters as carriers to prepare fully synthetic carbohydrate vaccines.
MATERIALS & METHODS: Gold glyconanoparticles bearing a synthetic tetrasaccharide epitope related to the Streptococcus pneumoniae type 14 capsular polysaccharide (Pn14PS), the T-helper ovalbumin 323-339 peptide (OVA(323-339)), and D-glucose were prepared by a one-pot method. Their immunogenicity was tested in mice. Cytokine levels after spleen cell stimulation with OVA(323-339) were analyzed using a luminex-multiplex cytokine assay. The capacity of the evoked antibodies to promote the uptake of S. pneumoniae type 14 by leukocytes was assessed.
RESULTS & DISCUSSION: Glyconanoparticles containing 45% of tetrasaccharide and 5% OVA(323-339) triggered specific anti-Pn14PS IgG antibodies. Cytokine levels confirmed that glyconanoparticles led to T-helper cell activation. The anti-saccharide antibodies promoted the phagocytosis of type 14 bacteria by human leukocytes, indicating the functionality of the antibodies.
Gold nanoparticles have great potential as carriers for the development of a great diversity of fully synthetic carbohydrate-based vaccines.
将病原体荚膜多糖与免疫原性蛋白载体（结合疫苗）偶联可提高碳水化合物免疫反应。我们的想法是探索金纳米簇作为载体来制备完全合成的碳水化合物疫苗。
采用一锅法制备了载有合成四糖表位的金糖纳米颗粒，该表位与肺炎链球菌 14 型荚膜多糖（Pn14PS）、卵清蛋白 T 辅助肽 323-339（OVA（323-339））和 D-葡萄糖有关。在小鼠中测试了它们的免疫原性。使用 luminex 多重细胞因子分析测定脾脏细胞经 OVA（323-339）刺激后的细胞因子水平。评估了诱导的抗体促进肺炎链球菌 14 型摄取白细胞的能力。
含有 45%四糖和 5% OVA（323-339）的糖纳米颗粒触发了特异性抗 Pn14PS IgG 抗体。细胞因子水平证实糖纳米颗粒导致 T 辅助细胞激活。抗多糖抗体促进了人白细胞对 14 型细菌的吞噬作用，表明了抗体的功能。
金纳米颗粒作为载体具有很大的潜力，可用于开发多种完全合成的基于碳水化合物的疫苗。
